The major objective is to elucidate mechanisms by which drugs and other chemicals alter functions of the thermoregulatory system, using simultaneous quantitative measurement at a variety of environmental temperatures of drug-induced changes in body temperature of restrained animals and of changes in thermoregulatory effector activities which cause or accompany these alterations of body temperature. Agents to be studied include histamine, morphine, lysergic acid diethylamide, tetrahydrocannabinols and/or marihuana. Initial studies with these agents involve recording of temperature in unrestrained cats provided with implemented thermocouples, iv catheters and/or intracerebral cannulas or guide tubes. A second objective is to assess possible roles of prostaglandins and cyclic AMP as intermediates in the production of hyperthermia by pyrogens and other agents. Investigations will also continue on the mechanisms of action of antipyretic agents with particular attention given to interactions between antipyretics and the release and activity of leukocytic pyrogen and to agents with possibly novel mechanisms of antipyretic action. BIBLIOGRAPHIC REFERENCES: Clark, W.G. & Cumby, H.R. Antagonism by antipyretics of the hyperthermic effect of a prostaglandin precursor, sodium arachidonate, in the cat. J. Physiol. 1976, in press. Clark, W.G. & Cumby, H.R. Biphasic changes in body temperature produced by intracerebroventricular injections of histamine in the cat. J. Physiol. 1976, in press.